Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations
Nicolas A, Sherva R, Grenier-Boley B, Kim Y, Kikuchi M, Timsina J, de Rojas I, Dalmasso MC, Zhou X, Le Guen Y, Arboleda-Bustos CE, Camargos Bicalho MA, et al.. Nature genetics, 2025-06-18
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
A polygenic score (PGS) for Alzheimer's disease (AD) was derived recently from data on genome-wide significant loci in European ancestry populations. We applied this PGS to populations in 17 European countries and observed a consistent association with the AD risk, age at onset and cerebrospinal fluid levels of AD biomarkers, independently of apolipoprotein E locus (APOE). This PGS was also associated with the AD risk in many other populations of diverse ancestries. A cross-ancestry polygenic risk score improved the association with the AD risk in most of the multiancestry populations tested when the APOE region was included. Finally, we found that the PGS/polygenic risk score captured AD-specific information because the association weakened as the diagnosis was broadened. In conclusion, a simple PGS captures the AD-specific genetic information that is common to populations of different ancestries, although studies of more diverse populations are still needed to better characterize the genetics of AD.
What this study adds
Evidence grade: High
This is a follow-up (cohort) study. A polygenic score derived from European data was associated with Alzheimer's risk, age at onset and biomarker levels in many other populations. Its stated limit: The authors state that studies of more diverse populations are still needed to better characterise AD genetics, and that an improvement seen in the Latin American Million Veteran Program group could not be distinguished from overfitting.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Nicolas, A., Sherva, R., Grenier-Boley, B., Kim, Y., Kikuchi, M., Timsina, J., et al. (2025). Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations. Nature genetics. https://doi.org/10.1038/s41588-025-02227-w
Vancouver
Nicolas A, Sherva R, Grenier-Boley B, Kim Y, Kikuchi M, Timsina J, et al. Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations. Nature genetics. 2025. doi:10.1038/s41588-025-02227-w. PMID: 40533518.
BibTeX
@article{nicolas2025-40533518,
author = {Nicolas, A. and Sherva, R. and Grenier-Boley, B. and Kim, Y. and Kikuchi, M. and Timsina, J. and de Rojas, I. and Dalmasso, M. C. and Zhou, X. and Le Guen, Y. and Arboleda-Bustos, C. E. and Camargos Bicalho, M. A. and others},
title = {{Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations}},
journal = {Nature genetics},
year = {2025},
doi = {10.1038/s41588-025-02227-w},
pmid = {40533518},
url = {https://doi.org/10.1038/s41588-025-02227-w}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- A polygenic score (PGS) for Alzheimer's disease (AD) was derived recently from data on genome-wide significant loci in European ancestry populations.
- This PGS was also associated with the AD risk in many other populations of diverse ancestries.
- Finally, we found that the PGS/polygenic risk score captured AD-specific information because the association weakened as the diagnosis was broadened.
- In conclusion, a simple PGS captures the AD-specific genetic information that is common to populations of different ancestries, although studies of more diverse populations are still needed to better characterize the genetics of AD.
Why it matters
A polygenic score derived from European data was associated with Alzheimer's risk, age at onset and biomarker levels in many other populations. This supports using such scores for risk assessment, not for treating or preventing the disease.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Study designcohort
- Evidence strengthHigh
Limitations
The authors state that studies of more diverse populations are still needed to better characterise AD genetics, and that an improvement seen in the Latin American Million Veteran Program group could not be distinguished from overfitting.
How this study scored 61/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 60 of the 98 points we could judge it on, which is 61 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature genetics) |
| Journal's citation record | 4 / 4 | Nature Genetics: journal h-index 776 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 22 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 12.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 22 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Bernardo de Mattos Viana: h-index 8 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Stanford University: institution h-index 2,684 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 113 institution(s) in 23 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40533518) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 60 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 60 of the 98 points we could judge it on is 61 out of 100. |
| Total | 61 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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